Tirofiban versus aspirin to prevent in-stent thrombosis after emergent carotid artery stenting in acute ischemic stroke.

BACKGROUND: Several antithrombotic treatments during emergent carotid artery stenting (eCAS) have been proposed, but an appropriate protocol to balance risk-benefit is not well known. OBJECTIVE: To investigate the efficacy and safety of tirofiban compared with aspirin in patients with acute ischemic stroke undergoing eCAS. METHODS: We conducted a retrospective single-center study of the prospective ARTISTA Registry, including patients with atherosclerotic internal carotid artery occlusion treated with eCAS. Two groups, according to antiplatelet drug, were studied: aspirin (250-500 mg single-dose) versus tirofiban (500 µg bolus+200 µg/h). Primary outcomes were the rate of in-stent thrombosis and symptomatic intracranial hemorrhage (sICH) within the first 24 hours. RESULTS: During the period 2019-2023, 181 patients were included, 103 received aspirin, 78 tirofiban; 149 (82.3%) had tandem lesions. The primary efficacy outcome occurred in 9 (9.4%) in the aspirin group, as compared with 1 (1.3%) in the tirofiban group (adjusted odds ratio (aOR)=0.11, 95% CI 0.01 to 0.98; P=0.048). The primary safety outcome was detected in 12 (11.7%) in the aspirin group, as compared with 2 (2.6%) in the tirofiban group (aOR=0.16, 95% CI 0.03 to 0.87; P=0.034). The tirofiban group presented a lower risk of parenchymal hemorrhage (18 (17.4%) vs 4 (5.2%), aOR=0.27, 95% CI 0.09 to 0.88; P=0.029) and an increased rate of excellent recanalization (expanded Treatment in Cerebral Infarction (eTICI) 2c-3) (50 (48.5%) vs 54 (69.2%); aOR=2.15, 95% CI 1.12 to 4.13; P=0.02). There were no differences in functional outcomes or mortality at 3 months. CONCLUSIONS: Periprocedural antithrombotic therapy with tirofiban was associated with a lower risk of in-stent thrombosis and sICH at 24 hours from eCAS compared with aspirin. Prospective randomized clinical trials are needed to confirm our results.

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Safety and efficacy of tirofiban in acute ischemic stroke due to tandem lesions undergoing mechanical thrombectomy: A multicenter randomized clinical trial (ATILA) protocol.

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.

Nurses' and midwives' perceptions and strategies to cope with perinatal death situations: A systematic literature review.

AIM: The aim of this paper is to describe the strategies used by nurses and midwives to cope with experiences of dealing with perinatal death and maintain their satisfaction at work. DESIGN: Systematic literature review, in accordance with the PRISMA Declaration. DATA SOURCES: (2000-2021) Web of Science, PubMed, Scopus, CINALH and Dialnet, for articles in English and Spanish from the period between January 2000 and March 2021. REVIEW METHODS: The outcome of the review was the perceptions of nurses and midwives who have cared for people in a situation of perinatal loss. RESULTS: Thirteen studies were identified that evaluated the attitudes, experiences and needs of these healthcare professionals. The combined size of all samples was 2196 participants. CONCLUSIONS: The negative effects on these professionals' satisfaction with their situation at work could be mitigated by covering their needs for knowledge, experience, and emotional and technical skills to deal with such events. IMPACT: As potential protective factors against dissatisfaction in nurses and midwives during perinatal death experiences, we identified older age and experience in perinatal care and coping strategies based on communicating one's feelings to peers, empathetic listening to the families cared for, training and institutional support. No Patient or Public Contribution.

Proximal sesamoid bone microdamage is localized to articular subchondral regions in Thoroughbred racehorses, with similar fracture toughness between fracture and controls.

OBJECTIVE: To determine whether proximal sesamoid bone (PSB) microdamage and fracture toughness differ between Thoroughbred racehorses sustaining PSB fracture and controls. STUDY DESIGN: Cadaveric case-control. ANIMALS: Twenty-four Thoroughbred racehorses (n = 12 PSB fracture, n = 12 control). METHODS: Proximal sesamoid bones were dissected, and gross pathological changes and morphological measurements were documented. High-speed exercise history data were evaluated. Microdamage was assessed in fracture, fracture-contralateral limb (FXCL) and control PSBs using whole bone lead uranyl acetate (LUA) staining with micro-CT imaging or basic fuchsin histological analysis. Fracture toughness mechanical testing was carried out in 3-point-bending of microbeams created from PSB flexor cortices. Data were analyzed using ordinal logistic and linear regression models. RESULTS: Microdamage was detected most commonly in the articular subchondral region of PSBs via LUA micro-CT and basic fuchsin histology. There were no differences in microdamage between FXCL and control PSBs. Fracture toughness values were similar for FXCL (1.31 MPa√m) and control (1.35 MPa√m) PSBs. Exercise histories were similar except that horses sustaining fracture spent a greater percentage of their careers in rest weeks. CONCLUSION: Microdamage was detected in the articular region of PSBs but was not greater in horses sustaining catastrophic PSB fracture. Fracture toughness of PSB flexor cortices did not differ between FXCL and control PSBs. CLINICAL SIGNIFICANCE: Although uncommon, microdamage is localized to the articular region of Thoroughbred racehorse PSBs. Catastrophic PSB failure is not associated with lower PSB flexor cortex fracture toughness.

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

Sleep-related hypermotor epilepsy with genetic diagnosis: description of a case series in a tertiary referral hospital.

INTRODUCTION: Sleep-related hypermotor epilepsy (SHE) is characterized by asymmetric tonic/dystonic posturing and/or complex hyperkinetic seizures occurring mostly during sleep. Experts agree that SHE should be considered a unique syndrome. PURPOSE: We present 8 cases of SHE for which a genetic diagnosis was carried out using a multigene epilepsy panel. METHODS: We retrospectively screened familial and isolated cases of SHE in current follow-ups in our center. RESULTS: We included 8 (5F/3M) patients, 5 of whom had a positive familial history of epilepsy. We identified a pathogenic mutation in CHRNA4, CHRNB2, and 3 different pathogenic changes in DEPDC5. CONCLUSIONS: Awareness of SHE needs to be raised, given its implications for finding an appropriate treatment, its relationship to cognitive and psychiatric comorbidities, and the opportunity to prevent the disorder in the descendants. We present our series with their clinical, radiological, electroencephalographic, and genetic characteristics, in which we found 3 pathogenic mutations in the DEPDC5 gene but not previously reported in the literature. Identifying new pathogenic mutations or new genes responsible for SHE will facilitate a better understanding of the disease and a correct genetic counseling.

Can servant leadership prevent hotel employee depression during the COVID-19 pandemic? A mediating and multigroup analysis.

The hospitality industry has been severely hit by the COVID-19 pandemic, with changes that have harmed employees' psychological well-being. However, having supervisors who are servant may make a difference. With a focus on serving others and the care taken to ensure their employees' highest priority needs are served, these leaders could help employees feel less depressed in these complicated times. By instilling servant behaviors in followers that help them become people that others can trust or with whom they can develop friendships, leaders could help these employees earn greater levels of personal social capital (PSC) through which to more successfully address pandemic times, especially if furloughed. Using structural equation modeling to analyze a sample of 205 hotel employees in Spain, we found that servant leadership directly decreases depression, and that PSC mediates this relationship. Our multigroup analyses (MGA) findings also reveal that when these employees are furloughed, the negative effect of PSC and the mediating role of PSC in this relationship is stronger. New light is thus shed on how servant leadership is effective in reducing employee depressive symptoms in times of severe changes such as those produced by the COVID-19 pandemic.

How Upper/Middle Managers' Ethical Leadership Activates Employee Ethical Behavior? The Role of Organizational Justice Perceptions Among Employees.

Several studies have been conducted on ethical leadership and workplace ethical behavior but little is known about the role of organizational justice and each of its dimensions (procedural, distributive, interpersonal, informational) in this relationship. This study predicts that ethical leadership enhances organizational justice perceptions, including each of its specific dimensions, which in turn enhances employee ethical behavior. The results from two-wave survey data obtained from 270 employees in the Malaysian manufacturing industry confirm that ethical leadership has a positive impact on employee ethical behavior, and that organizational justice and each of its justice dimensions mediate this relationship, both individually and together. Importantly, interpersonal and informational dimensions show the strongest mediation effects. This paper highlights the actions and strategies that can help managers to effectively elevate the moral tone in their organizations. In particular, our findings show where managers must put more emphasis to foster an ethical workplace: on providing fair treatment (interpersonal justice) and honest information (informational justice).

How Ethical Leadership Shapes Employees' Readiness to Change: The Mediating Role of an Organizational Culture of Effectiveness.

Today's organizations are operating in a highly competitive and changing environment that pushes them to continuously adapt their organizational structures to such environment. However, the success of change initiatives may face a barrier in the response of employees, especially when they lack readiness to change. While leadership can shape the culture of an organization and a culture of effectiveness can help increase employees' readiness to change, ethical leaders, who serve as a guide and offer support, can also make a difference by reducing uncertainty. Yet existing research on the role of ethical leadership in the enhancement of the employees' readiness to change is practically non-existent. Far less is the research that analyses the mechanisms that ethical leadership can use to foster employees' readiness to change. This study aims to investigate whether the ethical leadership of middle-lower echelons influences on employees' readiness to change positively (H1) and if this relationship is mediated through shaping an organizational culture of effectiveness (H2). Using data from 270 direct reports of middle-lower managers in public foreign trade Egyptian companies, the findings reveal that ethical leadership enhances employees' readiness to change and that this impact is partially mediated by an organizational culture of effectiveness. Thus, with these findings, new light is shed on the positive role of ethical leadership and the mechanisms it uses to enhance employees' readiness to change.

Altered Tissue Composition, Microarchitecture, and Mechanical Performance in Cancellous Bone From Men With Type 2 Diabetes Mellitus.

People with type 2 diabetes mellitus (T2DM) have normal-to-high BMDs, but, counterintuitively, have greater fracture risks than people without T2DM, even after accounting for potential confounders like BMI and falls. Therefore, T2DM may alter aspects of bone quality, including material properties or microarchitecture, that increase fragility independently of bone mass. Our objective was to elucidate the factors that influence fragility in T2DM by comparing the material properties, microarchitecture, and mechanical performance of cancellous bone in a clinical population of men with and without T2DM. Cancellous specimens from the femoral neck were collected during total hip arthroplasty (T2DM: n = 31, age = 65 ± 8 years, HbA1c = 7.1 ± 0.9%; non-DM: n = 34, age = 62 ± 9 years, HbA1c = 5.5 ± 0.4%). The T2DM specimens had greater concentrations of the advanced glycation endproduct pentosidine (+ 36%, P < 0.05) and sugars bound to the collagen matrix (+ 42%, P < 0.05) than the non-DM specimens. The T2DM specimens trended toward a greater bone volume fraction (BV/TV) (+ 24%, NS, P = 0.13) and had greater mineral content (+ 7%, P < 0.05) than the non-DM specimens. Regression modeling of the mechanical outcomes revealed competing effects of T2DM on bone mechanical behavior. The trend of higher BV/TV values and the greater mineral content observed in the T2DM specimens increased strength, whereas the greater values of pentosidine in the T2DM group decreased postyield strain and toughness. The long-term medical management and presence of osteoarthritis in these patients may influence these outcomes. Nevertheless, our data indicate a beneficial effect of T2DM on cancellous microarchitecture, but a deleterious effect of T2DM on the collagen matrix. These data suggest that high concentrations of advanced glycation endproducts can increase fragility by reducing the ability of bone to absorb energy before failure, especially for the subset of T2DM patients with low BV/TV. © 2019 American Society for Bone and Mineral Research.

The Impact of Anterior Glenoid Defects on Reverse Shoulder Glenoid Fixation in a Composite Scapula Model.

BACKGROUND: Achieving glenoid fixation with anterior bone loss can be challenging. Limited guidelines have been established for critical defect sizes that can be treated without supplemental bone graft when performing reverse shoulder arthroplasty. METHODS: We quantified the impact of two sizes of anterior glenoid defects on glenoid baseplate fixation in a composite scapula using the ASTM F 2028-14 reverse shoulder glenoid loosening test method. RESULTS: All glenoid baseplates remained well-fixed after cyclic loading in composite scapula without a defect and in scapula with an 8.5 mm anterior glenoid defect; however, one of seven baseplates loosened in a scapula with a 12.5 mm defect. No difference was observed between pre- and post-cyclic baseplate displacements in scapula with 8.5 mm or 12.5 mm defects or in the control group scapula. However, baseplate displacement in scapula with 12.5 mm anterior defects was significantly greater after cyclic loading than that of baseplates in 8.5 mm defects (superior-inferior displacement, p = 0.0004; anterior-posterior displacement, p < 0.0001), where baseplate displacement in 8.5 mm (superior- inferior displacement, p = 0.0003; anterior-posterior displacement, p = 0.0014) and 12.5 mm (superior-inferior displacement, p < 0.0001; anterior-posterior displacement, p < 0.0001) defects after cyclic loading was significantly greater than that of baseplates in scapula without a defect. DISCUSSION: Adequate and stable fixation can be achieved in scapula with anterior glenoid defects of at least 8.5 mm in this biomechanical model using an established testing methodology; however, supplemental bone grafting should be utilized for anterior glenoid defects of 12.5 mm and larger using the reverse shoulder prosthesis tested in this study.

New Strategies in the New Millennium: Servant Leadership As Enhancer of Service Climate and Customer Service Performance.

In a world in which customers are increasingly looking for solutions to their own concerns on how to make a better globalized world, new organizational strategies are emerging to approach the customer in the current third millennium. Servant leadership, which involves putting employees' needs first and serving the broader society, is emerging as a new strategic mechanism to approach the customer in line with the new social values-driven Marketing 3.0 era. Yet research has ignored the role and the various mechanisms servant leadership might utilize to improve customer service performance of their service units. Spanning 185 hotels located in Spain, a sample of 247 service units -in close contact with customers- was used to investigate whether servant leadership enhances customer service performance through shaping a service climate within the service unit. Results revealed that service climate mediates the positive influence of servant leadership on customer service performance. Managers can use these findings to note the value of leading the service unit in a servant friendly direction, which is better aligned with the new aspirations of customers today.

Consumer Participation in Co-creation: An Enlightening Model of Causes and Effects Based on Ethical Values and Transcendent Motives.

In the current highly interconnected modern world, the role of consumers has changed substantially due to their active collaboration with companies in product and process innovation. Specifically, consumer participation has become key to the development of successful products and services, as companies have come to rely more and more on consumers' opinion as a source of innovative ideas and brand value. However, whereas existing research has focused on identifying the different elements involved in consumers' co-creation, there is still the need to comprehend better this complex mechanism by integrating distinct dimensional insights. With an integrative review of research into three important perspectives, one nurturing from the Service-Dominant logic, another one based on the information and communication technologies (ICTs) platforms, and (the ethical values-driven) Marketing 3.0 paradigm, this article proposes a conceptual framework in which consumers' ethical values and transcendent motivations play an important role in encouraging their engagement in co-creation activities. In this connection, and with consumers increasingly embracing the need to fulfill a social and ethical function in society, the co-creation process is here comprehended as a means to emphasize the social and moral aspects of co-creation. This article also identifies the important, supportive role of the Marketing 3.0 paradigm and Web 3.0 tools to initiate the co-creation process, as well as the important valuable benefits attained by both companies and consumers after consumers engage in this process. Importantly, these benefits are highlighted to increase when ethical products are the object of these co-creation activities. All these insights have notable implications for both research and managerial practice.

Deposition of Ni nanoparticles onto porous supports using supercritical CO2: effect of the precursor and reduction methodology.

The deposition of Ni nanoparticles into porous supports is very important in catalysis. In this paper, we explore the use of supercritical CO(2) (scCO(2)) as a green solvent to deposit Ni nanoparticles on mesoporous SiO2 SBA-15 and a carbon xerogel. The good transport properties of scCO(2) allowed the efficient penetration of metal precursors dissolved in scCO(2) within the pores of the support without damaging its structure. Nickel hexafluoroacetylacetonate hydrate, nickel acetylacetonate, bis(cyclopentadienyl)nickel, Ni(NO(3))2⋅6H(2)O and NiCl(2)⋅6H(2)O were tried as precursors. Different methodologies were used: impregnation in scCO(2) and reduction in H(2)/N(2) at 400°C and low pressure, reactive deposition using H(2) at 200-250°C in scCO(2) and reactive deposition using ethanol at 150-200°C in scCO(2). The effect of precursor and methodology on the nickel particle size and the material homogeneity (on the different substrates) was analysed. This technology offers many opportunities in the preparation of metal-nanostructured materials.

Mass-transport Control on the Discharge Mechanism in Li-O2 Batteries Using Carbon Cathodes with Varied Porosity.

By comparing carbon electrodes with varying porosity in Li-O2 cells, we show that the effect of electrolyte stirring at a given current density can result in a change from 2D to 3D growth of discharged deposits. The change of morphology is evident using electron microscopy and by analyzing electrode pore size distribution with respect to discharge capacity. As a consequence, carbon electrodes with different textural properties exhibit different capacity enhancements in stirred-electrolyte cells. We demonstrate that mass transport can directly control the discharge mechanism, similar to the electrolyte composition and current density, which have already been recognized as determining factors.

Improved small molecule drug release from in situ forming poly(lactic-co-glycolic acid) scaffolds incorporating poly(ß-amino ester) and hydroxyapatite microparticles.

In situ forming implants are an attractive choice for controlled drug release into a fixed location. Currently, rapidly solidifying solvent exchange systems suffer from a high initial burst, and sustained release behavior is tied to polymer precipitation and degradation rate. The present studies investigated addition of hydroxyapatite (HA) and drug-loaded poly(ß-amino ester) (PBAE) microparticles to in situ forming poly(lactic-co-glycolic acid) (PLGA)-based systems to prolong release and reduce burst. PBAEs were synthesized, imbibed with simvastatin (osteogenic) or clodronate (anti-resorptive), and then ground into microparticles. Microparticles were mixed with or without HA into a PLGA solution, and the mixture was injected into buffer, leading to precipitation and creating solid scaffolds with embedded HA and PBAE microparticles. Simvastatin release was prolonged through 30 days, and burst release was reduced from 81 to 39% when loaded into PBAE microparticles. Clodronate burst was reduced from 49 to 32% after addition of HA filler, but release kinetics were unaffected after loading into PBAE microparticles. Scaffold dry mass remained unchanged through day 15, with a pronounced increase in degradation rate after day 30, while wet scaffolds experienced a mass increase through day 25 due to swelling. Porosity and pore size changed throughout degradation, likely due to a combination of swelling and degradation. The system offers improved release kinetics, multiple release profiles, and rapid solidification compared to traditional in situ forming implants.

On-line activity screening for radical scavengers from Baccharis chilco.

Baccharis plants have been used since ancient times in American traditional medicine. Baccharis chilco is a perennial shrub of temperate regions of South America that grows well in rainfall forests of Colombia. Neither chemical composition nor biological studies of this plant have ever been reported. Two caffeoylquinic acid (CQA) derivatives, 5-O-[(E)-caffeoyl]quinic acid (1) and 3,5-di-O-[(E)-caffeoyl]quinic acid (3), and rosmarinic acid (2) have been isolated from B. chilco growing wild in Colombia, using the on-line HPLC-DAD-DPPH radical-scavenging detection technique as guidance. In the course of the purification work, L-chiro-inositol (4) was also isolated. Structures of the four isolated compounds were determined by spectroscopic methods. Antioxidants 2 and 3 exhibited high antiradical activities evaluated by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(.)) assay, although somewhat lower than that of the reference compound ascorbic acid. The on-line HPLC-DAD-DPPH technique allowed a rapid pinpointing of antioxidants in the studied EtOH extract, and the facile guided isolation of the target molecules.